URINARY EXCRETION OF d-TUBOCURARINE IN MAN

¹ Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada

d-Tubocurarine was extracted from urine with ethylene dichloride. A shift of its ultraviolet absorption which depended on pH was used for the determination.

The urinary excretion of d-tubocurarine was measured after intravenous, subcutaneous and intramuscular (in oil) injections into normal human subjects. The excretion after intravenous injection of 5 mgm. lasted more than 18 hours. Independent of dose and mode of administration about one-third of the amounts injected were excreted.

The excretion curves after intravenous injection were not simple exponential curves. An attempt was therefore made to describe the excretion curves by postulating velocity constants for the passage from blood to tissue and from tissue to blood as well as for renal excretion and destruction.

By assuming an additional velocity constant for the passage from the site of injection into the blood, the excretion curves after subcutaneous injection could be mathematically described. The excretion curve after intramuscular injection in oil could not be described, probably because the disappearance of tubocurarine from an oily depot is not a simple function of drug concentration.

Using Teorell's equations with the postulated velocity constants, a graph representing the fate of tubocurarine in man after intravenous injection was constructed. The graph permitted an interpretation of a number of experimental observations.